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Multifunctional Cytoskeleton Network in Human Diseases: Mutual Risk of Dementia,...
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Multifunctional Cytoskeleton Network in Human Diseases: Mutual Risk of Dementia, Cancer and COVID-19

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Motility and Adhesion".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 15206

Special Issue Editors

Prof. Dr. Judit Ovádi

E-Mail Website1 Website2
Guest Editor
Institute of Enzymology, Research Centre for Natural Sciences, H‐1117 Budapest, Hungary
Interests: unstructured proteins; physiological and patologycal protein interactions; multifunctional microtubule network; Tubulin Polymerization Promoting Protein (TPPP/p25); neomorphic moonlighting proteins; special chameleon feature; drug targeting
Dr. Judit Oláh

E-Mail Website
Guest Editor
Institute of Enzymology, Research Center for Natural Sciences, Eötvös Loránd Research Network, H-1117 Budapest, Hungary
Interests: cytoskeletal microtubule network; TPPP/p25

Special Issue Information

Dear Colleagues,

The sensing, integrating, and coordinating features of eukaryotic cells are achieved by complex ultrastructural arrays and multifarious functions of the cytoskeleton, including the microtubule network. The diverse functions of microtubules playing crucial roles are regulated by their decoration with proteins/enzymes, as well as post-translational modifications.  Microtubules are essential for cell polarity, cell shape, differentiation, cell division, and intracellular transport, as well as for autophagy and pathological inclusion body formation. Moreover, the essential role of the cytoskeleton has been established in host–virus interactions. Coronaviruses interact with specific constituents of the cytoskeleton to promote internalization of the virus into host cells. At a later stage of the virus life cycle, SARS-CoV-2 uses motor proteins on the microtubules and actin filaments for its transport within the cell.

Tubulin-polymerization-promoting protein (TPPP/p25) is a microtubule-associated protein displaying both physiological and pathological functions. Physiologically, moonlighting TPPP/p25 modulates the dynamics and stability of the microtubule network by bundling the microtubules and enhancing their acetylation level. The enhancement of the acetylation of microtubules due to the direct binding of TPPP/p25 to HADC6 and Sirt2 counteracts with the uncontrolled mitosis of the cells. In addition, TPPP/p25 forms toxic oligomers/aggregates with alpha-synuclein in neurons and oligodendrocytes in the cases of Parkinson's disease and multiple system atrophy, respectively. All these findings reveal the antimitotic and alpha-synuclein aggregation-promoting potency of TPPP/p25, consistent with the finding that Parkinson’s disease patients have a reduced risk for certain cancers.

The mechanism of development of many human diseases is not yet fully elucidated, the understanding of which favors the evolvement of their treatments. Critical problems, however, are that a single disease might originate from defects of multiple genes/proteins affecting the same pathway, while the defects of the same gene/protein can cause different diseases. These genes can interact with different proteins, forming multifunctional complexes, which display a crucial role in both physiological and pathological processes, including human development, etiology of neurological disorders, cancer, and infection. Functional alterations of the macromolecular complexes take place in the case of COVID-19, as well. For example, long-lasting neurological symptoms after COVID-19 infection may occur, although their interrelationship is yet unclear. 

This Special Issue aims to elucidate the high complexity of genes and/or proteins, their molecular pathogeny associated with human diseases, and their potential interrelationships. These topics might unify specialized researchers, bringing together the latest key findings and historical advances in this hot research area, including the components of the cytoskeleton and their function in human diseases. A greater understanding of the etiologies of these diseases will lead to the discovery of new diagnostic and therapeutic applications.

Prof. Dr. Judit Ovádi
Dr. Judit Oláh
Guest Editors

Manuscript Submission Information

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Keywords

  • coronaviruses
  • viral infection
  • cytoskeletal microtubules
  • cytoskeleton
  • physiological and pathological interactions
  • transmission and trafficking
  • drug targeting
  • dementia
  • cancer
  • COVID-19

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Published Papers (3 papers)

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Review

22 pages, 974 KiB  
Review
A Defective Viral Particle Approach to COVID-19
by Maria Kalamvoki and Vic Norris
Cells 2022, 11(2), 302; https://doi.org/10.3390/cells11020302 - 17 Jan 2022
Cited by 9 | Viewed by 3765
Abstract
The novel coronavirus SARS-CoV-2 has caused a pandemic resulting in millions of deaths worldwide. While multiple vaccines have been developed, insufficient vaccination combined with adaptive mutations create uncertainty for the future. Here, we discuss novel strategies to control COVID-19 relying on Defective Interfering [...] Read more.
The novel coronavirus SARS-CoV-2 has caused a pandemic resulting in millions of deaths worldwide. While multiple vaccines have been developed, insufficient vaccination combined with adaptive mutations create uncertainty for the future. Here, we discuss novel strategies to control COVID-19 relying on Defective Interfering Particles (DIPs) and related particles that arise naturally during an infection. Our intention is to encourage and to provide the basis for the implementation of such strategies by multi-disciplinary teams. We therefore provide an overview of SARS-CoV-2 for a multi-disciplinary readership that is specifically tailored to these strategies, we identify potential targets based on the current knowledge of the properties and functions of coronaviruses, and we propose specific strategies to engineer DIPs and other interfering or therapeutic nanoparticles. Full article
(This article belongs to the Special Issue Multifunctional Cytoskeleton Network in Human Diseases: Mutual Risk of Dementia, Cancer and COVID-19)
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13 pages, 1379 KiB  
Review
Host Cell and SARS-CoV-2-Associated Molecular Structures and Factors as Potential Therapeutic Targets
by Jitendra Kumar Chaudhary, Rohitash Yadav, Pankaj Kumar Chaudhary, Anurag Maurya, Rakesh Roshan, Faizul Azam, Jyoti Mehta, Shailendra Handu, Ramasare Prasad, Neeraj Jain, Avaneesh Kumar Pandey and Puneet Dhamija
Cells 2021, 10(9), 2427; https://doi.org/10.3390/cells10092427 - 15 Sep 2021
Cited by 5 | Viewed by 5604
Abstract
Coronavirus disease 19 (COVID-19) is caused by an enveloped, positive-sense, single-stranded RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the realm Riboviria, order Nidovirales, family Coronaviridae, genus Betacoronavirus and the species Severe acute [...] Read more.
Coronavirus disease 19 (COVID-19) is caused by an enveloped, positive-sense, single-stranded RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the realm Riboviria, order Nidovirales, family Coronaviridae, genus Betacoronavirus and the species Severe acute respiratory syndrome-related coronavirus. This viral disease is characterized by a myriad of varying symptoms, such as pyrexia, cough, hemoptysis, dyspnoea, diarrhea, muscle soreness, dysosmia, lymphopenia and dysgeusia amongst others. The virus mainly infects humans, various other mammals, avian species and some other companion livestock. SARS-CoV-2 cellular entry is primarily accomplished by molecular interaction between the virus’s spike (S) protein and the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), although other host cell-associated receptors/factors, such as neuropilin 1 (NRP-1) and neuropilin 2 (NRP-2), C-type lectin receptors (CLRs), as well as proteases such as TMPRSS2 (transmembrane serine protease 2) and furin, might also play a crucial role in infection, tropism, pathogenesis and clinical outcome. Furthermore, several structural and non-structural proteins of the virus themselves are very critical in determining the clinical outcome following infection. Considering such critical role(s) of the abovementioned host cell receptors, associated proteases/factors and virus structural/non-structural proteins (NSPs), it may be quite prudent to therapeutically target them through a multipronged clinical regimen to combat the disease. Full article
(This article belongs to the Special Issue Multifunctional Cytoskeleton Network in Human Diseases: Mutual Risk of Dementia, Cancer and COVID-19)
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Graphical abstract

10 pages, 1408 KiB  
Review
Role of Multifunctional Cytoskeletal Filaments in Coronaviridae Infections: Therapeutic Opportunities for COVID-19 in a Nutshell
by Victor Norris and Judit Ovádi
Cells 2021, 10(7), 1818; https://doi.org/10.3390/cells10071818 - 19 Jul 2021
Cited by 6 | Viewed by 4069
Abstract
A novel coronavirus discovered in 2019 is a new strain of the Coronaviridae family (CoVs) that had not been previously identified in humans. It is known as SARS-CoV-2 for Severe Acute Respiratory Syndrome Coronavirus-2, whilst COVID-19 is the name of the disease [...] Read more.
A novel coronavirus discovered in 2019 is a new strain of the Coronaviridae family (CoVs) that had not been previously identified in humans. It is known as SARS-CoV-2 for Severe Acute Respiratory Syndrome Coronavirus-2, whilst COVID-19 is the name of the disease associated with the virus. SARS-CoV-2 emerged over one year ago and still haunts the human community throughout the world, causing both healthcare and socioeconomic problems. SARS-CoV-2 is spreading with many uncertainties about treatment and prevention: the data available are limited and there are few randomized controlled trial data on the efficacy of antiviral or immunomodulatory agents. SARS-CoV-2 and its mutants are considered as unique within the Coronaviridae family insofar as they spread rapidly and can have severe effects on health. Although the scientific world has been succeeding in developing vaccines and medicines to combat COVID-19, the appearance and the spread of new, more aggressive mutants are posing extra problems for treatment. Nevertheless, our understanding of pandemics is increasing significantly due to this outbreak and is leading to the development of many different pharmacological, immunological and other treatments. This Review focuses on a subset of COVID-19 research, primarily the cytoskeleton-related physiological and pathological processes in which coronaviruses such as SARS-CoV-2 are intimately involved. The discovery of the exact mechanisms of the subversion of host cells by SARS-CoV-2 is critical to the validation of specific drug targets and effective treatments. Full article
(This article belongs to the Special Issue Multifunctional Cytoskeleton Network in Human Diseases: Mutual Risk of Dementia, Cancer and COVID-19)
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